Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrotic syndrome (NS) is characterized by proteinuria, oxidative stress and endogenous hyperlipidemia. Hyperlipidemia and oxidative stress may be involved in coronary heart disease and the progression of renal damage in these patients. Garlic has been suggested to be beneficial in various disease states. Some of the beneficial effects of garlic may be secondary to its hypolipidemic and antioxidant properties. Therefore, the effect of a 2% garlic diet on acute and chronic experimental NS induced by puromycin aminonucleoside (PAN) was studied in this work. Acute NS was induced by a single injection of PAN to rats which were sacrificed 10 days later. Chronic NS was induced by repeated injections of PAN to rats which were sacrificed 84 days after the first injection. Garlic treatment was unable to modify proteinuria in either acute or chronic NS, and hypercholesterolemia and hypertriglyceridemia in acute NS. However, garlic treatment diminished significantly total-cholesterol, LDL-cholesterol and triglycerides, but not HDL-cholesterol in chronic NS. Garlic induced no change in the percentage of sclerotic glomeruli in chronic NS and a significative decrease on the percentage of sclerotic area of these glomeruli (33 +/- 3% in NS+Garlic group vs. 47 +/- 4% in NS group, p = 0.0126). The enhanced in vivo renal H2O2 production and the diminished renal Cu, Zn-SOD and catalase activities in acute NS, and the decreased renal catalase activity in chronic NS were not prevented by garlic treatment. These data indicate that garlic treatment ameliorates hyperlipidemia and renal damage in chronic NS which is unrelated to proteinuria or antioxidant enzymes.
Mol Cell Biochem 2000 Aug
PMID:Garlic ameliorates hyperlipidemia in chronic aminonucleoside nephrosis. 1105 49

Rat HDL are known to increase testosterone production by cultured Leydig cells either following gonadotropin stimulation or cholesteryl ester depletion. However, rat HDL contain apolipoprotein E and have a high affinity for the members of the low density receptor family such as LDL receptor, LDL receptor related protein and VLDL receptor. In contrast with the adrenal cells, the contribution of apo A-I and apo E pathways in HDL cholesterol uptake has not been yet evidenced in rat Leydig cells. Recent data provided evidence that hCG stimulates scavenger receptor BI expression in testes. In order to investigate if testosterone production can be stimulated by apo E depleted HDL, we compared the level of testosterone stimulation by HDL with or without apo E first, in presence of saturating dose of hCG (1 IU/ml) and second, after depletion of cholesterol synthesis by pravastatin, an inhibitor of HMG-CoA reductase. In presence of hCG, HDL with or without apo E increased testosterone production respectively by 37 and 25%. Pravastatin at 100 microg/ml inhibited the cholesterol synthesis and the testosterone production by 25% and decreased the cholesteryl content by 25%. The addition of HDL with or without apo E (50 microg protein HDL/ ml) completely overcame the depletion of cellular cholesteryl esters and the inhibition of testosterone production induced by pravastatin. In the presence of heparin, apo E depleted HDL overcame the testosterone production induced by pravastatin, indicating that uptake of HDL without apo E via a secretion of apo E by the cells themselves was not involved. Therefore, in absence of apo E, it is suggested that rat Leydig cells used HDL to regulate steroidogenesis via an apolipoprotein A-I pathway.
Mol Cell Biochem 2000 Oct
PMID:Rat Leydig cells use apolipoprotein E depleted high density lipoprotein to regulate testosterone production. 1112 58

Dunnigan-type familial partial lipodystrophy (FPLD; OMIM 151660) is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes, dyslipidemia, and hypertension. Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. The findings in FPLD indicate that defective structure of the nuclear envelope produces a phenotype of insulin resistance. The findings may have relevance for common insulin resistance and for drug-associated lipodystrophies, whose molecular basis is unknown at present.
Mol Genet Metab 2000 Dec
PMID:Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. 1113 44

Progesterone (P) is a mineralocorticoid (MC)-antagonist in vitro. During pregnancy, plasma P concentrations exceed aldosterone concentrations at least 50-fold, but plasma aldosterone increases only 4-8-fold in a compensatory manner. Since the in vivo anti-MC activity of P seems to be only moderate, we hypothesized that P is metabolized by enzymes of MC target tissue similar to the way cortisol is metabolized by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2 in order to protect the MC receptor. We, therefore, examined P metabolism using 4-(14)C-P in subcellular fractions of human postmenopausal and male kidneys, and in homogenates of one premenopausal kidney. We found that P is converted effectively, even at high P concentrations (10(-6) mol/l), to various metabolites: 20alpha-dihydro(DH)-P; 17alpha-OH-P; 17alpha-OH,20alpha-DH-P; 5alpha-DH-P; 3beta,5alpha-tetrahydro(TH)-P; and 20alpha-DH,5alpha-DH-P. Homogenates of premenopausal kidney also showed conversion to 3alpha- and 5beta-reduced P metabolites. These results confirm the existence of an efficient renal enzyme system as a possible mechanism of an enzyme-mediated MC receptor selectivity.
Mol Cell Endocrinol 2001 Jan 22
PMID:Enzyme-mediated protection of the mineralocorticoid receptor against progesterone in the human kidney. 1116 7

The genetic predisposition for cardiovascular disease seems to play an important role in atherogenesis. Atherosclerosis, which can be clinically asymptomatic for many years, begins early in life. Therefore finding markers of early atherosclerotic process would be of great importance for screening and early treatment of these children. As the result of endothelial dysfunction, the adhesion molecules (VCAM-1, ICAM-1, ELAM) are overexpressed. These molecules are shed from the surface and can be measured, as soluble forms in serum. Therefore they can be regarded as early markers of atherosclerosis. The aim of the study was to measure the serum levels of soluble adhesion molecules ELAM, ICAM-1, VCAM-1 and plasma lipid profile--total (TC), LDL (LDL-C) and HDL-cholesterol (HDL-C) and triglycerides (TG) in children from families of high risk for cardiovascular diseases. Forty-eight children were studied, 24 children from high risk families, according to NCEP definition: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). Twenty-four healthy children without familial history of cardiovascular disease were used as the control. Children of either group did not have any metabolic diseases. The concentration of sELAM, sICAM-1 and sVCAM-1 were assessed using ELISA kits. Soluble ICAM-1 level was significantly higher in high risk group in comparison to control (p<0.02). The soluble VCAM-1 and ELAM levels did not differ significantly between the groups. There were no changes in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides between the groups. In normolipidemic children from families with high risk for atherosclerosis the soluble ICAM-1 levels are significantly higher as compared to control.
Int J Mol Med 2001 Feb
PMID:Soluble ICAM-1, VCAM-1 and E-selectin in children from families with high risk of atherosclerosis. 1117 23

Apolipoprotein D (ApoD) constitutes an atypical lipoprotein in so far as it is predominantly found associated with HDL particles but belongs to the lipocalin structural family. Apart from its involvement in serum lipid transport it is abundant in various tissues, and differing physiological functions have been ascribed to it. We have now developed an E. coli expression system that permits the efficient production of biochemically homogeneous ApoD via secretion into the bacterial periplasm. Detailed ligand binding studies by fluorescence titration revealed that progesterone and arachidonic acid are complexed with dissociation constants both in the 1 microM range, whereas the presumed ligands pregnenolone, bilirubin and E-3M2H are not recognized by the recombinant protein. In contrast with previous reports it thus appears that ApoD discriminates well in its binding function between closely related compounds.
J Mol Recognit
PMID:Bacterially produced apolipoprotein D binds progesterone and arachidonic acid, but not bilirubin or E-3M2H. 1118 May 64

11beta-hydroxysteroid dehydrogenase (11beta-HSD) regulates local actions of corticosteroids at glucocorticoid and mineralocorticoid receptors. Corticosteroids are thought to play important roles in ocular function. However, mechanisms of intraocular corticosteroid action are still unclear. Therefore, in this study, we examined the immunohistochemical localization of 11beta-HSD type 1 (11beta-HSD1), 11beta-HSD type 2 (11beta-HSD2), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in human ocular tissues from patients (6 months to 78 years of age; n = 10) retrieved from surgical pathology files. Both 11beta-HSD2 and MR immunoreactivity was detected only in non-pigmented epithelium of the ciliary body, but was undetectable in cornea, lens, iris, retina, choroid and sclera, in all the cases examined. GR was detected in all cell types in the human eye. 11beta-HSD1 immunoreactivity was not detected in the human eye in this study. These results suggest that 11beta-HSD2 play an important role in human ocular mineralocorticoid action, such as the production of aqueous humor, in the ciliary body. The widespread expression of GR suggests that glucocorticoids may play an important role in the function and homeostasis of the human eye.
Mol Cell Endocrinol 2001 Feb 28
PMID:Immunohistochemical distribution of 11beta-hydroxysteroid dehydrogenase in human eye. 1122 83

The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes catalyze the interconversion of active glucocorticoids (GC) with their inert metabolites, thereby regulating the functional activity of GC. While 11beta-HSD type 1 (11beta-HSD1) activates GC from their 11-keto metabolites, 11beta-HSD type 2 (11beta-HSD2) inactivates GC. Here we report that both of these enzymes are expressed in human aortic smooth muscle cells (SMC), and that 11beta-HSD1 is more abundant and is differentially regulated relative to 11beta-HSD2. Stimulation of SMC with IL-1beta or TNFalpha led to a time- and dose-dependent increase of mRNA levels for 11beta-HSD1, while 11beta-HSD2 mRNA levels decreased. Parallel enzyme activity studies showed increased conversion of 3H-cortisone to 3H-cortisol but not 3H-cortisol to 3H-cortisone, demonstrating 11beta-HSD1 in SMC acts primarily as a reductase. A similar increase of 11beta-HSD1 mRNA expression was also found in human bronchial SMC upon stimulation, indicating the regulatory effect is not limited to vascular smooth muscle. Additional parallel studies revealed a similar pattern of induction for 11beta-HSD1 and monocyte chemoattractant protein-1, a well-defined proinflammatory molecule. These data suggest 11beta-HSD1 may play an important role in regulating inflammatory responses in the artery wall and lung.
J Steroid Biochem Mol Biol 2001 May
PMID:Induction of 11beta-hydroxysteroid dehydrogenase type 1 but not -2 in human aortic smooth muscle cells by inflammatory stimuli. 1137 76

The activity of the enzyme lecithin-cholesterol acyltransferase (LCAT; E.C. 2.3.1.43) is involved in the removal of cholesterol excess from peripheral cells. This activity is stimulated by the HDL (high density lipoprotein) apolipoprotein A1 (ApoA1). Haptoglobin (Hpt) was previously found to be associated with ApoA1 in ovarian follicular fluid. LCAT activity was analyzed in follicular fluids, collected from an IVF program, containing different amounts of Hpt or Hpt/ApoA1 ratio. Addition of purified Hpt to follicular fluid caused a decrease in the enzyme activity, which was measured as the rate of synthesis of cholesteryl esters. In the fractions of fluid proteins, as obtained by gel filtration chromatography, Hpt and HDL were titrated by ELISA while the LCAT activity was assayed by using radioactive cholesterol and purified HDL. When isolated LCAT was incubated with fractions containing different Hpt/ApoA1 ratios, the enzyme activity was found negatively correlated with the Hpt/ApoA1 ratio (P < 0.01). LCAT kinetic parameters were measured in two fractions with the same amount of ApoA1 (5 microg/ml) but different amounts of Hpt (0.69 or 3.77 microg/ml): the V(max) did not change while the K(m) values were 24.1 or 78.6 microM in the presence of the low or high Hpt level, respectively. The analysis of fluids associated with cytoplasmically mature MII oocytes, in a cross-sectional study, confirmed that a negative correlation exists between the Hpt/ApoA1 ratio and the LCAT activity (P < 0.01). The results suggest that Hpt inhibits the reverse transport of cholesterol by preventing ApoA1 stimulation of the LCAT activity.
Mol Reprod Dev 2001 Jun
PMID:Haptoglobin inhibits lecithin-cholesterol acyltransferase in human ovarian follicular fluid. 1138 53

We have shown mouse to be an useful animal model for studies on the estrogen-mediated synthesis and secretion of lipoproteins since, unlike in rats, low density lipoprotein receptors are not upregulated in mice. This results into the elevation of plasma levels of apolipoprotein (apo) B and apoE, and lowering of apoA-1-containing particles. The mechanisms of apoB and apoE elevation by estrogen have been elucidated, but the mechanism of lowering of plasma levels of HDL is still not known. Among other factors, apoA-I, cholesterol ester transfer protein (CETP), scavenger receptor B1 (SR-B1), and hepatic lipase are potential candidates that modulate plasma levels of HDL. Since estrogen treatment increased hepatic apoA-I mRNA and apoA-I synthesis, and mouse express undetectable levels of CETP, we tested the hypothesis that estradiol-mediated lowering of HDL in mice may occur through modulation of hepatic lipase (HL). Four mouse strains (C57L, C57BL, BALB, C3H) were administered supraphysiological doses of estradiol, and plasma levels of HDL as well as HL mRNA were quantitated. In all 4 strains estradiol decreased plasma levels of HDL by 30%, and increased HL mRNA 2-3 fold. In a separate experiment groups of male C57BL mouse were castrated or sham-operated, and low and high doses of estradiol administered. We found 1.4-2.5 fold elevation of HL mRNA with concomitant lowering of HDL levels. Ten other mouse strains examined also showed estradiol-induced elevation of HL mRNA, but the extent of elevation was found to be strain-specific. Based on these studies, we conclude that hepatic lipase is an important determinant of plasma levels of HDL and that HL mRNA is modulated by estrogen which in turn may participate in the lowering of plasma levels of HDL.
Mol Cell Biochem 2001 Apr
PMID:Estrogen increases hepatic lipase levels in inbred strains of mice: a possible mechanism for estrogen-dependent lowering of high density lipoprotein. 1145 87


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